[Protective effect of forsythiaside A on acute lung injure induced by lipopolysaccharide in mice].

Abstract

OBJECTIVE: To study the potential protective effect of monomer forsythiaside A (FA), a key component of traditional Chinese medicine, on acute lung injury induced by lipopolysaccharide (LPS) in mice and its possible mechanism. METHODS: The mouse model of acute lung injury was induced by LPS of 10 mg/kg, ip. The experiment was carried out in six groups: control group: without any treatment (n=8); acute lung injury model group: mice were given LPS at a dose of 10 mg/kg (n=8); antibody group: mice were given anti-TLR4/MD antibody (50 μg/20 g body weight) 12 h before modeling (n=8); high-, medium- and low-dose FA groups: mice were respectively given FA at 80 mg/kg (n=8), 20 mg/kg (n=8) and 5 mg/kg (n=8). Mice in all FA treatment groups were given FA once a day till 7 days before modeling. Blood and lung tissue specimens were taken 4 h after modeling. Amount of endotoxin in plasma was measured by kinetic turbidimetric assay. Degree of lung damage was graded by HE staining. Expression of TLR4 at both mRNA and protein levels were measured by RT-PCR and Western blotting, respectively. Expressions of MyD88 and NF-κB were detected by immunohistochemistry. Content of TNF-α in serum was detected by ELISA. RESULTS: Compared with the control group, endotoxin and TNF-α in the model group significantly increased (P<0.01), with obvious pathological damages in lung tissue, such as thickened alveolar septum, hyperemia, edema and infiltration of a lot of neutrophils. Compared with the model group, FA groups presented significantly decreased endotoxin level (P<0.01), attenuated lung damages, down-regulated expressions of TLR4 mRNA and protein, MyD88 and NF-κB proteins in the lung (P<0.01), and significantly dropped TNF-α content in plasma (P<0.01). In addition, the protective effect of FA was dose dependent. CONCLUSION: FA has a protective effect on acute lung injury induced by LPS in mice. The mechanism may be related to the interference in LPS-TLR4-MyD88-NF-κB signaling pathway.